Category Archives: Effects of Methoxamine and Epinephrine

Our finding of improved cerebral blood flow with methoxamine contrasts sharply with a recent report by Brown et al who found no significant improvement with methoxamine in a pig cardiac arrest model. However, blood flow results reported in their study reveal small but definite increments in organ flow as the methoxamine dose was increased. The contrasting findings are perhaps best explained by differences in the timing of microsphere flow determinations following drug administration. Brown et al performed one flow determination very shortly after a single bolus administration of the drug and may not have observed the maximal effect of methoxamine. Indeed, we clearly saw increases in the mean organ flow drug effect between 5-minute measurements and the 20-minute values following methoxamine. buy antibiotics online

However, if the mechanism of improved survival with higher BPs is simply better myocardial blood flow during CPR, we would expect to observe higher myocardial blood flow values in the methoxamine group (6/6 survivors) than with high-dose epinephrine (1/6 survivors). However, right and left ventricular mean blood flow values during CPR were similar with methoxamine and high-dose epinephrine. One possible explanation for this finding is that our group size was too small to detect the difference in myocardial blood flow. This is to some extent supported by the observation that the sole survivors in each epinephrine group were those individual animals with the highest BPs and myocardial flows during CPR. A further possibility, previously suggested by other investigators, is that while BP and resultant myocardial flow are important determinants of survival, the level of myocardial oxygen consumption is also important. Since epinephrine, but not methoxamine, has been shown to increase myocardial oxygen consumption, it may be that even though high-dose epinephrine resulted in right and left ventricular flows similar to those achieved by methoxamine, increased 02 consumption offset this effect and led to greater ischemic injury and poorer survival. asthma inhalers

Brown et al have already demonstrated improved cerebral blood flow within the first few minutes following IV administration of high-dose epinephrine in pigs undergoing CPR. Our findings concur, although we also demonstrated a marked reduction in CO with high-dose epinephrine that was most obvious beyond 17 minutes following initial drug administration. Several factors may account for the difference. The one microsphere flow determination by Brown et al was completed within 4lA minutes after single bolus administration of the drug. Since our animals received repeated boluses, it might well be that circulating epinephrine levels in our high-dose epinephrine group were much higher. Interspecies variability must also be considered.

Therefore, we elected to standardize timing, frequency, and distance above the sternum for piston readjustment in this study to minimize variability in provision of CCCM. Another potential problem we considered was baseline hemodynamic status, since individual differences in hydration, for example, might also lead to differences in the efficacy of CCCM or response to drugs. Accordingly, prior to performing baseline measurements, dogs were volume loaded with 6 percent hetastarch solution where necessary to ensure a Pw of 6 ± 1 mm Hg, and as a consequence differences in baseline hemodynamics were minimized. ventolin inhalers

Methoxamine compared favorably with both high-dose epinephrine and low-dose epinephrine in several respects. Methoxamine was associated with higher aortic diastolic and mean BP during CPR and resulted in better survival. Although both methoxamine and high-dose epinephrine yielded similar values for cerebral blood flow during CPR, survival with high-dose epinephrine remained poor. An unanticipated finding was the marked reduction in CO following the use of high-dose epinephrine in comparison to placebo or methoxamine. birth control pills

In addition there was a strong association between diastolic BP achieved during CCCM and subsequent successful resuscitation. This is illustrated in Figure 3, in which diastolic BP in survivors is seen to be significantly higher (44 ±3.4 SD) than in nonsurvivors (21 ±2.7 SD). ventolin inhaler
As with survival, higher BP was strongly associated with higher cerebral and myocardial blood flow values. There were positive linear correlations between mean BP and cerebral blood flow (r=.70) and diastolic BP and left ventricular flow (r=.70). These comparisons were selected on the assumptions that cerebral blood flow would be dependent on mean BP and coronary blood flow would be dependent on diastolic BP during CPR.

Prearrest hemodynamics, arterial blood gases, and hematocrit levels were not different (Table 1). Successful resuscitation from VF, as defined above, was significantly more frequent in the dogs receiving methoxamine than in the other three treatment groups (Table 2). Five of the six survivors receiving methoxamine converted to sinus rhythm after the first defibrillation attempt, and all maintained an adequate BP for more than one hour without further intervention. No ventricular arrhythmias were noted in this group following successful resuscitation.

Because of chest deformation occurring in most dogs, piston arm distance was readjusted ten minutes into the arrest. The CCCM was maintained for a full 25 minutes without any adjustment of ventilation or of the Thumper except for the uniformly applied adjustment at ten minutes, noted above. The study drugs were administered as previously noted, and the only other intervention included IV administration of 0.5 mEq/kg of sodium bicarbonate (Na-HC03) given IV at 15 minutes. Throughout this time, airway pressure, thoracic aortic pressure, and ECG were continuously recorded. Arterial and mixed venous blood samples were obtained at 5, 10, 15, 20, and 25 minutes, and analyzed for Po2, Pco2, pH, and hematocrit. Microsphere flow determinations were performed beginning at five minutes and 20 minutes after induction of VF.

Prior to baseline measurements all dogs were allowed a period of about one hour to ensure steady state. During this time Pw was adjusted to 6± 1 mm Hg by iniusion of 6 percent hetastarch solution if necessary and the ventilator was adjusted to ensure adequate ventilation and oxygenation. Baseline measurements, including all pressure measurements, arterial and mixed venous blood gases, and radionuclide-labeled microsphere determinations of CO and organ blood flow were then performed. The dogs were then assigned by random draw to receive one of the following four treatments to begin three minutes after VF had been induced: group 1, low-dose epinephrine, 0.02 mg/kg intravenous (IV) bolus every three minutes; group 2, high-dose epinephrine, 0.2 mg/kg IV bolus every three minutes; group 3, methoxamine, 20 mg IV single bolus at three minutes; and group 4, placebo control (PC), equal volume normal saline solution every three minutes. buy ortho tri-cyclen

To ensure that all microspheres injected had passed into the peripheral circulation by the time the withdrawal was completed, another 3 ml of blood was also drawn from the thoracic aorta into a separate syringe immediately after collection of the reference sample, and this was subsequently processed along with the reference sample to detect the presence of microspheres. flovent inhaler
On completion of the experiment, the following tissues were removed and weighed for the determination of regional blood flow at the time of each microsphere injection: the entire right and left cerebral hemispheres, entire brain stem, and samples (>10 g total from at least five sites) of temporalis muscle and left and right ventricular free walls.